Molecular mechanism of pancreatic alpha cell failure in type 2 diabetes

Research Project

Project/Area Number	25293208
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Partial Multi-year Fund
Section	一般
Research Field	Metabolomics
Research Institution	Gunma University
Principal Investigator	KITAMURA TADAHIRO 群馬大学, 生体調節研究所, 教授 (20447262)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000) Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000) Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000) Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords	グルカゴン / Sirt1 / 膵α細胞 / 糖尿病 / α細胞 / FoxO1 / ATF3
Outline of Final Research Achievements	Pancreatic alpha cell dysfunction as well as beta cell dysfunction is known to be important for pathophysiology of type 2 diabetes. However, its molecular mechanism has been unclear. Thus, we generated both knockout mice and knockin mice in which Sirt1, an NAD-dependent deacetylase and a cellular energy sensor, lack or overexpress specifically in alpha cells. The metabolic profiles and histological analysis revealed that Sirt1 negatively regulates alpha cell differentiation/proliferation, and positively regulates glucose-dependent glucagon secretion.

Report

(4 results)